Keen on discovering novel ways to tackle viral infections, AIS Biotech, a French company based in the Alps, aims to combat influenza, more commonly known as the flu, by leveraging the medicinal promise behind glycobiotechnology.
A field that has been gaining momentum over the past decade, glycobiotechnology is the study of complex carbohydrates which has multifaceted applications in various fields including medicine, and is emerging as a frontier in transforming the landscape of bioscience.
Carbohydrates, which are long chains of polysaccharides that are broken down by the body to produce energy, can be converted to create renewable energy, in a bid to lower our dependence on fossils, as it is the largest source of biomass on the planet. And more recently, its therapeutic potential has been grabbing attention.
For instance, the breakdown of carbohydrates, accelerated by microbial enzymes, can not only be used to generate biomaterials but also pharmaceutical products. And to add to that, it could become a compelling method to fight infectious diseases.
Battling the flu
Affecting nearly five million people worldwide, according to the World Health Organization (WHO), the influenza virus is a seasonal epidemic that is characterized by chills, a sore throat, runny nose, body aches and fatigue. With over 500,000 deaths recorded yearly, severe cases can be fatal, particularly for those who have respiratory disorders, and are considered to be high risk.
Founded a mere four months ago, AIS Biotech’s – where AIS stands for Anti-Infective Sugar – mission is to not simply treat these illnesses but to prevent them. For this, the startup has developed its drug candidate GlycoFlu.
As the influenza virus enters the host cell by binding to a specific site on the surfaces of glycoproteins and glycolipid receptors of the host – after which, through the cellular process of endocytosis, the cell gulps the virus before it replicates itself – GlycoFlu is designed to thwart the initial binding process.
The drug candidate is able to mimic the natural host surface oligosaccharide binding-site of Influenza viruses. As a result, it is capable of neutralizing the virus and preventing the attachment to host cell-surface complex sugars acting as receptors for cell infection, explained Aurelie Juhem, CEO of AIS Biotech.
Juhem believes that curbing infection by saturating the pathogen’s receptors with synthetic oligosaccharides in order to inhibit the initial infection step – which is the binding of the pathogen to the host cell surface – is the way to go.
“Cell surface oligosaccharides are the target of many pathogens,” said Juhem. “In our case, to develop our strategy for preventing infections, glycobiotechnology is a sustainable way to produce our tailor-made carbohydrate bioproducts that are the specific active ingredients of our innovative anti-infectives.”
AIS Biotech: on the path towards sustainable pharma
The young biotech has teamed up with the Center for Research on Plant Macromolecules CERMAV-CNRS for the development of GlycoFlu, which also aims to promote the production of environmentally friendly biopharmaceutical products. As the pharmaceutical industry is responsible for generating tens of thousands of metric tons of chemical waste, bioproducts like GlycoFlu could be a more sustainable alternative, to confront this looming problem.
Juhem expressed that she was impressed by the highly efficient, cost-effective bioproduction process with lower environmental impacts when compared to chemical processes.
“As a biologist, I’ve always been motivated by projects with a potential to impact patients in a positive way, and biotechnology is one of the most dynamic and innovative sectors. Indeed, in the last years, many scientific and technological advancements came from biotechnology, and in a large panel of applications such as energy, health, agriculture and food that are big challenges faced by the society,” said Juhem.
Although GlycoFlu is a nascent technology and is still in the making, carbohydrate-based drugs have been around since the 1940s. Antibiotics like streptomycin and neomycin have been used to treat numerous bacterial infections including tuberculosis. The former works by disrupting the function of ribosomes – which is the site where protein synthesis takes place in a cell – in bacterial cells, which is similar to neomycin’s mechanism of action. And apart from these antibiotics, chemotherapy drugs like doxorubicin, more popularly known under its brand name Adriamycin, consists of a deoxy sugar obtained from a certain strain of Streptomyces bacteria. It halts the growth of cancer cells by blocking the enzyme topo isomerase 2, and is used in the treatment of various kinds of cancers including leukemia, lymphoma, neuroblastoma, sarcoma and Wilms tumor, among others.
However, these anti-infectives and anticancer drugs are regarded as treatments against diseases and not preventative measures, unlike GlycoFlu.
Currently in preclinical stages, GlycoFlu has undergone a proof of concept study in influenza models both in vivo – having examined a mouse model with the infection – as well as as ex vivo – on a human airway epithelium. Besides this, the company is advancing its analytical methods and scale-up manufacturing process.
Could AIS Biotech’s GlycoFlu target other infectious diseases?
While AIS Biotech’s attempt to target SARS-CoV-2 did not attain desirable results, as the sialosides (complex sugars) produced to create GlycoFlu is designed to only mimic those targeted by influenza viruses, the startup has identified other pathogens – which are yet to be disclosed as it is still being investigated – that can bind to sugar-based receptors. This means that the technology could become a wider platform addressing medical needs of patients affected by infectious diseases, through this novel mechanism. Juhem also pointed out that to specifically target a pathogen, say for example coronavirus, they have to prepare different bacterial strains that are able to produce sialosides correlating to the virus.
Presently funded via bank loans, grants and personal investment, Juhem hopes that their first fundraiser, which is scheduled to take place soon, will aid in achieving the company’s first milestone.
“AIS Biotech’s mission is to contribute to the fight against current and emerging infectious diseases,” said Juhem. “My hope for the future, as AIS Biotech’s CEO, is that GlycoFlu and our next drug-candidates will be effective in humans to contribute to the constant fight against current and emerging diseases.”